Gestational diabetes is a common pregnancy complication. Although the precise underlying mechanism has yet to be identified, insulin resistance and inadequate insulin secretion to compensate for it play a central role in the pathophysiology of GDM. Excess adiposity is an important modifiable risk factor for the development of the condition. Mechanisms linking excess adiposity to elevated risk of GDM are not completely understood, but recent evidence points to the crucial role of specific hormones and cytokines (adipokines) secreted by the adipose tissue. The general goal of this project is for research on the pathogenesis of GDM. Under this research theme, the specific aim of this project is to prospectively investigate novel biochemical markers, for instance, biomarkers involved in adipocyte cytokine secretion and metabolism in association with subsequent risk of GDM and fetal overgrowth. This project utilizes bio-specimens from throughout pregnancy from GDM cases and matched controls within the NICHD Fetal Growth Studies. In the past year, we actively worked with the UMN laboratory to obtain data including non-targeted metabolomics data from UC Davis. We are teaming with biostatiticians analyzing the data. Statistical analyses and manuscript preparation on biomarkers of GDM risk are ongoing. Publications have focused on modifiable biomarkers and metabolomics and lipodomic profiling that are functions of major exogenous origin (via dietary intake). For example, we recently provided one of the first lines of evidence suggesting that circulating concentrations of saturated fatty acids varying by chain length, as early as the first trimester, were associated with subsequent risk of GDM. In addition, recent work has focused on hormone levels and GDM risk such as our work providing evidence that thyroid function early in pregnancy may be an indicator for subsequent risk of GDM. We identified novel lipid species associated with GDM risk and observed different association pattern by lipid class, acyl chain carbon number and double bond number, and the timing of lipid measurement during pregnancy. Lastly, we recently published findings suggesting a potential important clinical utility of HbA1c measurement in the first trimester of pregnancy, even among low-risk women. While our findings require replication, GDM prediction was significantly improved with the inclusion of HbA1c over conventional risk factors suggesting that it could be used to improve early risk-stratification and screening in women with elevated levels.